Mollified hyperbolic method for coefficient identification problems

AbstractWe introduce a stable numerical method for the identification of a transmissivity coefficient in a one-dimensional parabolic equation. It is a combination of the Mollification Method and a well-known space marching implementation of the Hyperbolic Regularization procedure. The new method succesfully restores a certain type of continuity with respect to the initial condition and the boundary data. The accuracy of the algorithm is demonstrated by means of several examples where exact and perturbed data are considered

Liquid Hydrogen Target Experience at SLAC

Liquid hydrogen targets have played a vital role in the physics program at SLAC for the past 40 years. These targets have ranged from small "beer can" targets to the 1.5 m long E158 target that was capable of absorbing up to 800 W without any significant density changes. Successful use of these targets has required the development of thin-wall designs, liquid hydrogen pumps, remote positioning and alignment systems, safety systems, control and data acquisition systems, cryogenic cooling circuits and heat exchangers. Detailed operating procedures have been created to ensure safety and operational reliability.This paper surveys the evolution of liquid hydrogen targets at SLAC and discusses advances in several of the enabling technologies that made these targets possible

A range of catalytic efficiencies with avian retroviral protease subunits genetically linked to form single polypeptide chains

Molecular modeling based on the crystal structure of the Rous sarcoma virus (RSV) protease dimer has been used to link the two identical subunits of this enzyme into a functional, single polypeptide chain resembling the nonviral aspartic proteases. Six different linkages were selected to test the importance of different interactions between the amino acids at the amino and carboxyl termini of the two subunits. These linkages were introduced into molecular clones of fused protease genes and the linked protease dimers were expressed in Escherichia coli and purified. Catalytically active proteins were obtained from the inclusion body fraction after renaturation. The linked protease dimers exhibited a 10-20-fold range in catalytic efficiencies (V(max)/K(m)) on peptide substrates. Both flexibility and ionic interactions in the linkage region affect catalytic efficiency. Some of the linked protease dimers were 2-3-fold more active than the nonlinked enzyme purified from bacteria, although substrate specificities were unchanged. Similar relative efficiencies were observed using a polyprotein precursor as substrate. Mutation of one catalytic Asp in the most active linked protease dimer inactivated the enzyme, demonstrating that these proteins function as single polypeptide chains rather than as multimers

Monte Carlo study of the critical temperature for the planar rotator model with nonmagnetic impurities

We performed Monte Carlo simulations to calculate the Berezinskii-Kosterlitz-Thouless (BKT) temperature $T_{BKT}$ for the two-dimensional planar rotator model in the presence of nonmagnetic impurity concentration $(\rho)$. As expected, our calculation shows that the BKT temperature decreases as the spin vacancies increase. There is a critical dilution $\rho_c \approx 0.3$ at which $T_{BKT} =0$. The effective interaction between a vortex-antivortex pair and a static nonmagnetic impurity is studied analytically. A simple phenomenological argument based on the pair-impurity interaction is proposed to justify the simulations.Comment: 5 pages, 5 figures, Revetex fil

Urine culture testing in community nursing homes: Gateway to antibiotic overprescribing

OBJECTIVE To describe current practice around urine testing and identify factors leading to overtreatment of asymptomatic bacteriuria in community nursing homes (NHs) DESIGN Observational study of a stratified random sample of NH patients who had urine cultures ordered in NHs within a 1-month study period SETTING 31 NHs in North Carolina PARTICIPANTS 254 NH residents who had a urine culture ordered within the 1-month study period METHODS We conducted an NH record audit of clinical and laboratory information during the 2 days before and 7 days after a urine culture was ordered. We compared these results with the urine antibiogram from the 31 NHs. RESULTS Empirical treatment was started in 30% of cases. When cultures were reported, previously untreated cases received antibiotics 89% of the time for colony counts of ≥100,000 CFU/mL and in 35% of cases with colony counts of 10,000-99,000 CFU/mL. Due to the high rate of prescribing when culture results returned, 74% of these patients ultimately received a full course of antibiotics. Treated and untreated patients did not significantly differ in temperature, frequency of urinary signs and symptoms, or presence of Loeb criteria for antibiotic initiation. Factors most commonly associated with urine culture ordering were acute mental status changes (32%); change in the urine color, odor, or sediment (17%); and dysuria (15%). CONCLUSIONS Urine cultures play a significant role in antibiotic overprescribing. Antibiotic stewardship efforts in NHs should include reduction in culture ordering for factors not associated with infection-related morbidity as well as more scrutiny of patient condition when results become available

Deletion of Sirt3 does not affect atherosclerosis but accelerates weight gain and impairs rapid metabolic adaptation in LDL receptor knockout mice: implications for cardiovascular risk factor development.

Sirt3 is a mitochondrial NAD(+)-dependent deacetylase that governs mitochondrial metabolism and reactive oxygen species homeostasis. Sirt3 deficiency has been reported to accelerate the development of the metabolic syndrome. However, the role of Sirt3 in atherosclerosis remains enigmatic. We aimed to investigate whether Sirt3 deficiency affects atherosclerosis, plaque vulnerability, and metabolic homeostasis. Low-density lipoprotein receptor knockout (LDLR(-/-)) and LDLR/Sirt3 double-knockout (Sirt3(-/-)LDLR(-/-)) mice were fed a high-cholesterol diet (1.25 % w/w) for 12 weeks. Atherosclerosis was assessed en face in thoraco-abdominal aortae and in cross sections of aortic roots. Sirt3 deletion led to hepatic mitochondrial protein hyperacetylation. Unexpectedly, though plasma malondialdehyde levels were elevated in Sirt3-deficient mice, Sirt3 deletion affected neither plaque burden nor features of plaque vulnerability (i.e., fibrous cap thickness and necrotic core diameter). Likewise, plaque macrophage and T cell infiltration as well as endothelial activation remained unaltered. Electron microscopy of aortic walls revealed no difference in mitochondrial microarchitecture between both groups. Interestingly, loss of Sirt3 was associated with accelerated weight gain and an impaired capacity to cope with rapid changes in nutrient supply as assessed by indirect calorimetry. Serum lipid levels and glucose tolerance were unaffected by Sirt3 deletion in LDLR(-/-) mice. Sirt3 deficiency does not affect atherosclerosis in LDLR(-/-) mice. However, Sirt3 controls systemic levels of oxidative stress, limits expedited weight gain, and allows rapid metabolic adaptation. Thus, Sirt3 may contribute to postponing cardiovascular risk factor development

Can Sepsis Be Detected in the Nursing Home Prior to the Need for Hospital Transfer?

Objectives: To determine whether and to what extent simple screening tools might identify nursing home (NH) residents who are at high risk of becoming septic. Design: Retrospective chart audit of all residents who had been hospitalized and returned to participating NHs during the study period. Setting and Participants: A total of 236 NH residents, 59 of whom returned from hospitals with a diagnosis of sepsis and 177 who had nonsepsis discharge diagnoses, from 31 community NHs that are typical of US nursing homes overall. Measures: NH documentation of vital signs, mental status change, and medical provider visits 0–12 and 13–72 hours prior to the hospitalization. The specificity and sensitivity of 5 screening tools were evaluated for their ability to detect residents with incipient sepsis during 0–12 and 13–72 hours prior to hospitalization: The Systemic Inflammatory Response Syndrome criteria, the quick Sequential Organ Failure Assessment (SOFA), the 100-100-100 Early Detection Tool, and temperature thresholds of 99.0°F and 100.2°F. In addition, to validate the hospital diagnosis of sepsis, hospital discharge records in the NHs were audited to calculate SOFA scores. Results: Documentation of 1 or more vital signs was absent in 26%–34% of cases. Among persons with complete vital sign documentation, during the 12 hours prior to hospitalization, the most sensitive screening tools were the 100-100-100 Criteria (79%) and an oral temperature >99.0°F (51%); and the most specific tools being a temperature >100.2°F (93%), the quick SOFA (88%), the Systemic Inflammatory Response Syndrome criteria (86%), and a temperature >99.0°F (85%). Many SOFA data points were missing from the record; in spite of this, 65% of cases met criteria for sepsis. Conclusions: NHs need better systems to monitor NH residents whose status is changing, and to present that information to medical providers in real time, either through rapid medical response programs or telemetry

Comparison of the substrate-binding pockets of the Rous sarcoma virus and human immunodeficiency virus type 1 proteases

A steady state kinetic analysis of the avian myeloblastosis virus/Rous sarcoma virus (AMV/RSV) and human immunodeficiency virus Type 1 (HIV-1) retroviral proteases (PRs) was carried out using a series of 40 peptide substrates that are derivatives of the AMV/RSV nucleocapsid-PR cleavage site. These peptides contain single amino acid substitutions in each of the seven positions of the minimum length substrate required by the PR for specific and efficient cleavage. These peptide substrates are distinguished by the individual enzyme subsites of the AMV/RSV and HIV-1 PRs. The molecular basis for similarities and differences of the individual subsites for both proteases is discussed using steady state kinetic data and modeling based on crystal structures

Mechanism of inhibition of the retroviral protease by a Rous sarcoma virus peptide substrate representing the cleavage site between the gag p2 and p10 proteins

The activity of the avian myeloblastosis virus (AMV) or the human immunodeficiency virus type 1 (HIV-1) protease on peptide substrates which represent cleavage sites found in the gag and gag-pol polyproteins of Rous sarcoma virus (RSV) and HIV-1 has been analyzed. Each protease efficiently processed cleavage site substrates found in their cognate polyprotein precursors. Additionally, in some instances heterologous activity was detected. The catalytic efficiency of the RSV protease on cognate substrates varied by as much as 30-fold. The least efficiently processed substrate, p2- p10, represents the cleavage site between the RSV p2 and p10 proteins. This peptide was inhibitory to the AMV as well as the HIV-1 and HIV-2 protease cleavage of other substrate peptides with K(i) values in the 5-20 μM range. Molecular modeling of the RSV protease with the p2-p10 peptide docked in the substrate binding pocket and analysis of a series of single-amino acid- substituted p2-p10 peptide analogues suggested that this peptide is inhibitory because of the potential of a serine residue in the P1' position to interact with one of the catalytic aspartic acid residues. To open the binding pocket and allow rotational freedom for the serine in P1', there is a further requirement for either a glycine or a polar residue in P2' and/or a large amino acid residue in P3'. The amino acid residues in P1-P4 provide interactions for tight binding of the peptide in the substrate binding pocket